Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Δευτέρα 28 Νοεμβρίου 2016

Systemic Light Chain Amyloidosis Mimicking Rheumatic Disorders

Secondary amyloidosis can complicate chronic inflammatory autoimmune diseases. However, the clinical findings of primary amyloidosis may mimic those of primary rheumatologic disorders. We present the case of a 53-year-old woman who presented with dystrophic nail changes, dry eyes, bilateral carpal tunnel syndrome, Raynaud's phenomenon, and high titer positive nucleolar pattern antinuclear antibody. She was initially misdiagnosed as having Undifferentiated Connective Tissue Disease (UCTD). On further workup, she was eventually diagnosed with lambda light chain systemic amyloidosis by abdominal fat pad biopsy. Her symptoms completely resolved after autologous stem cell transplantation. With this case, we would like to highlight the similarities in the clinical features between light chain amyloidosis and rheumatological disorders. We would also like to emphasize the importance of the prompt recognition of the clinical features of amyloidosis which are crucial to triggering appropriate diagnostic procedures, since early diagnosis is a key to improving outcomes in this disease with an otherwise poor prognosis.

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The Influence of Timing and Frequency of Adipose-derived Mesenchymal Stem Cell Therapy on Immunomodulation Outcomes after Vascularized Composite Allotransplantation.

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Background: Cellular therapies for immunomodulation in vascularized composite allotransplantation (VCA) have gained importance due to their potential minimization of immunosuppression. Adipose-derived mesenchymal stem cells (AD-MSCs) especially have shown encouraging potential. We investigated the influence of timing and frequency of AD-MSC-treatment on immunologic and graft survival as well as graft vasculopathy (GV) outcomes after VCA. Methods: Lewis (LEW) rats received full-mismatched Brown Norway (BN) rat hindlimb transplants. Recipient animals were assigned to groups receiving donor-derived AD-MSCs (106 cells/animal) either on postoperative day (POD) 1, POD 4, or repeatedly on POD 4, 8, and 15, and compared to untreated controls. Results: While AD-MSC administration on POD 1 or POD 4,8,15 resulted in 50% long-term graft acceptance, recipients treated on POD 4 and controls rejected prior to POD 50. All treated animals revealed peripheral blood chimerism (4 weeks), most pronounced following repetitive cell administration (12.92% vs. 5.03% [POD 1] vs. 6.31% [POD 4]; p

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Checks and balances - microbiota shifts in immunosuppressed mice.

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No abstract available

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The Presence of Pretransplant HLA Antibodies Does Not Impact the Development of Chronic Lung Allograft Dysfunction or CLAD Related Death.

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Background: Development of Donor-specific Antibodies (DSA) after lung transplantation is associated with antibody mediated rejection (AMR), acute cellular rejection, and bronchiolitis obliterans syndrome (BOS); however, the significance of circulating antibodies before transplant remains unclear. Methods: We performed a retrospective cohort study including recipients of primary lung transplants between 2008 and 2012.We assessed the impact of circulating human leukocyte (HLA) and noncytotoxic Donor Specific antibodies (DSA) detected before transplant on development of Chronic Lung Allograft Dysfunction (CLAD) or CLAD related death. Results: 30% of subjects had circulating class I antibodies alone, 4% Class II, and 14.4% class I and class II at MFI > 1000. 9% of subjects had DSA Class I, 9% Class II and 2.4% both DSA Class 1 and 2. Neither the presence of circulating antibodies (adjusted HR 0.87; 95% CI 0.50 - 1.54 p=0.65) nor the presence of DSA (adjusted HR 1.56; 95% CI 0.77 - 3.18) before transplant at MFI > 1000 was associated with the development of CLAD or CLAD related death. Conclusions: While in previous studies we have shown an increased incidence of AMR in patients with pretransplant DSA, neither the presence of HLA antibodies nor DSA translated to an increased risk of allograft dysfunction or death if prospective crossmatch testing was negative. Prospective studies are needed to define the impact of pretransplant sensitization on lung transplant recipients. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Biomarkers for Cardiac Allograft Vasculopathy: Still Searching After All These Years.

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No abstract available

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Immunological Risk Stratification by Assessing both the HLA and non-HLA Specific Antibodies: Time to Include Testing for Non-HLA Antibodies in the Routine Clinical Antibody Analysis Profile?.

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No abstract available

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Differential role of B cells and IL-17 versus IFN-[gamma] during early and late rejection of pig islet xenografts in mice.

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Background: Xenogeneic islet transplantation is an emerging therapeutic option for diabetic patients. However, immunological tolerance to xenogeneic islets remains a challenge. Methods: The current study used a pig-to-mouse discordant xenogeneic islet transplant model to examine anti-donor xenogeneic immune responses during early and late rejection, and to determine experimental therapeutic interventions that promote durable pig islet xenograft survival. Results: We found that during early acute rejection of pig islet xenografts, the rejecting hosts exhibited a heavy graft infiltration with B220+ B cells and a robust anti-pig antibody production. In addition, early donor-stimulated IL-17 production, but not IFN-[gamma] production, dominated during early acute rejection. Recipient treatment with donor apoptotic 1-ethyl-3-(3'-dimethylaminopropyl)-carbodiimide-treated splenocytes (ECDI-SP) significantly inhibited anti-donor IL-17 response, and when combined with B cell depletion and a short course of rapamycin led to survival of pig islet xenografts beyond 100 days in ~65% recipients. Interestingly, treated recipients in this model experienced late rejection between 100 - 200 days posttransplant, which coincided with B cell reconstitution and an ensuing emergence of a robust anti-donor IFN-[gamma], but not IL-17, response. Conclusions: These findings reveal that early and late rejection of pig islet xenografts may be dominated by different immune responses, and that maintenance of long-term xenogeneic tolerance will require strategies that target the temporal sequence of anti-xenogeneic immune responses. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Induction Therapy, Rejection and Graft Outcomes in Paediatric and Adolescent Kidney Transplant Recipients.

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Background: Although the clinical benefit of interleukin-2-receptor antibody (IL-2RAb) induction in reducing the risk of acute rejection in adult kidney transplant recipients is well established, a similar benefit in paediatric recipients remains controversial. The aim of this study is to evaluate the efficacy of IL-2RAb in reducing acute rejection in paediatric and adolescent recipients aged

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Necroptosis is Involved in CD4+ T cell Mediated Microvascular Endothelial Cell Death and Chronic Cardiac Allograft Rejection.

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Background: Despite advances in immunosuppressive therapies, the rate of chronic transplant loss remains substantial. Organ injury involves various forms of cell death including apoptosis and necrosis. We now recognize that early injury of cardiac transplants involves a newly described form of programmed necrotic cell death, termed necroptosis. As this involves receptor-interacting protein kinase (RIP) 1/3, this study aimed to establish the role of RIP3 in chronic cardiac allograft rejection. Method: We used MHC class II mismatched C57BL/6N (H-2b; B6) or B6.RIP3-/- (H-2b; RIP3-/-) mice to B6.C-H-2bm12 (H2-Ab1bm12; bm12) mouse cardiac transplantation. Microvascular endothelial cells (MVEC) were developed from B6 and RIP3-/- cardiac grafts. Result: CD4+ T cell-mediated cardiac graft rejection is inhibited using RIP3 deficient donor grafts, with reduced cellular infiltration and vasculopathy compared with wild type cardiac grafts. Allo-reactive CD4+ T cells-mediated MVEC death involves tumor necrosis factor [alpha] (TNF[alpha]), Fas ligand (FasL) and granzyme B. While necroptosis and release of danger molecule high-mobility group box 1 (HMGB1) are eliminated by the absence of RIP3, CD4+ T cells had attenuated MVEC death through granzyme B and FasL. Conclusion: CD4+ T cell-mediated MVEC death involves in TNF[alpha], FasL and granzyme B. Necroptotic cell death and release of the danger molecule may promote inflammatory responses and transplant rejection. While loss of RIP3 does not eliminates allo-immune responses, chronic graft injury is reduced. RIP3 is an important therapeutic target but additional granzyme and caspases inhibition is required for sufficiently improving long term graft survival. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Absence of miR-182 Augments Cardiac Allograft Survival.

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Background: MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate the posttranscriptional expression of target genes and are important regulators in immune responses. Previous studies demonstrated that the miRNA, miR-182 was significantly increased during allograft rejection. Further, the transcription factor Forkhead box (FOX) protein 1, (FOXO1) was shown to be a target of miR-182. The aim of this study is to further examine the role of miR-182 in alloimmune responses. Methods: Transplantation of BALB/c cardiac allografts was performed in C57BL/6, miR-182-/-, B6.129S-H2dlAb1-Ea (MHC II- and CD4+ T cell-deficient) and B6.129S2-Tap1tm1Arp (MHC I- and CD8+ T cell-deficient) mice, with or without CTLA-4Ig administration. T cell phenotype, FOXO1 protein levels and graft infiltrating lymphocytes were determined in C57BL/6 or miR-182-/- mice by flow cytometric analysis, western blot and immunohistochemistry, respectively. Results: We now show that T cells, mainly CD4+ are the main cellular source of miR-182 during allograft rejection. In the absence of miR-182, CTLA-4Ig treatment significantly increased allograft survival (31.5 days C57BL/6 vs. 60 days miR-182-/-, P

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Altered pharyngeal structure and dynamics among patients with cervical kyphosis

Objectives/Hypothesis

Deformities of the anterior cervical spine are an established cause of dysphagia. Whereas osteophytes and spinal fusion hardware have been reported to alter bolus flow and contribute to swallowing dysfunction, the relationship between abnormal spine curvature and swallowing dysfunction is not established. The purpose of this investigation was to evaluate the association between cervical kyphosis and objective measures of swallowing dysfunction on videofluoroscopy.

Study Design

Case-control study of patients presenting to tertiary dysphagia center.

Methods

All videofluoroscopic swallow studies (VFSS) performed at our institution, between August 1, 2014, and August 1, 2015, were retrospectively reviewed to identify patients with abnormal cervical kyphosis, according to Cobb and Jackson angle measurements. Patients with kyphosis were age- and gender-matched to persons without kyphosis. VFSS and demographic parameters were collected and compared between groups.

Results

Thirty-six patients with cervical kyphosis exceeding two standard deviations (SD) beyond established age-specific normal ranges were identified. The mean age of the entire cohort was 61.6 (SD ±19.1) years. Mean pharyngeal area was 3.34 cm2 greater in kyphosis patients compared to controls (95% confidence interval [CI]: 0.47-5.21 cm2; P = .0007). This was associated with increased hypopharyngeal transit time (0.57 seconds, 95% CI: 0.045-1.09 seconds, P = .034), and higher prevalence of penetration (P = .014). There was no significant difference in the pharyngeal constriction ratio (PCR), a surrogate measure of pharyngeal strength (P = .83).

Conclusions

Patients with cervical spine kyphosis have a significantly dilated pharynx (P = .0007), elongated hypopharyngeal transit time (P = .034), and worsened penetration aspiration scores (P = .021). Absence of a difference in PCR suggests adequate compensation as a group.

Level of Evidence

3b. Laryngoscope, 2016



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PPARγ targeted oral cancer treatment and additional utility of genomics analytic techniques

Objective

Peroxisome proliferator-activated receptor γ (PPARγ) agonists have been shown to have anti-proliferative, anti-angiogenic, and proapoptotic effects, leading to interest in their use as cancer therapeutics. Pioglitazone, a U.S. Food and Drug Administration-approved type II diabetes medication and PPARγ agonist, may have a role in adjuvant head-and-neck squamous cell carcinoma treatment or prevention. Therefore, the purpose of this study was: 1) to treat oral cavity cancer cells with the PPARγ activator, pioglitazone, to analyze gene expression changes; and 2) to compare those changes with our preexisting genomic data for development of hypothesis-driven additional basic and clinical studies.

Study Design

Prospective in vitro.

Methods

We utilized microarray technology, as well as OCPlus (Bioconductor open source software) and Ingenuity Pathway Analysis (Qiagen, Redwood City, CA), to analyze differential gene expression in tumor and pioglitazone-treated tumor cells on a genome-wide level to demonstrate the feasibility of such an approach and determine appropriate sample size for future investigations.

Results

We found that approximately 35 samples are required to adequately power future studies. We next discovered that pioglitazone significantly affects Inducible T-Cell Costimulator (iCOS)-Ligand for the T-cell-specific cell surface receptor ICOS (iCOSL) and type II diabetes mellitus pathways as a putative anti-cancer mechanism.

Conclusion

Genome-wide analysis is possible for the exploration of differential pathway modulation and rapid hypothesis generation. Both inflammation and type II diabetes pathways were significantly altered and therefore might provide unique hypothesis-driven pharmacodynamic parameters for future in vitro or in vivo studies utilizing thiazolidinediones. These techniques could be applied to microarray or other high throughput data from a variety of hypothesis-generating research scenarios in otolaryngology (e.g., middle ear proteomics, sinus microbiome studies).

Level of Evidence

NA. Laryngoscope, 2016



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What is the preferred perioperative antibiotic choice and duration of use following major head and neck surgery?



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Interleukin (IL)-6 modulates transforming growth factor -β receptor I and II (TGF-βRI and II) function in epidermal keratinocytes

Abstract

It been shown that IL-6 modulates TGF-β1 expression in fibroblasts, however; what role IL-6 plays concerning TGF-βR expression and function in skin is unknown. Therefore, the aim of this study was to investigate the mechanism by which IL-6 might modulates TGF-β receptors in skin.

Skin from WT, IL-6 overexpressing mice, and IL-6 treated keratinocyte cultures were analyzed for TGF-βRI and TGF-βRII expression via histology, PCR, and flow cytometry. Receptor function was assessed by cell migration, bromodeoxyuridine (BrdU) proliferation assays, and Smad7 expression and Smad2/3 phosphorylation. Receptor localization within the membrane was determined by co-immunoprecipitation.

IL-6 overexpression and treatment increased TGF-βRII expression in the epidermis. IL-6 treatment of keratinocytes induced TGF-βRI and II expression, and augmented TGF-β1-induced function as demonstrated through increased migration and decreased proliferation. Additionally, IL-6 treatment of keratinocytes altered receptor activity as indicated by altered Smad2/3 phosphorylation and increased Smad7 and membrane localization.

These results suggest that IL-6 regulates keratinocyte function by modulating TGF-βRI and II expression and signal transduction via trafficking of the receptor to lipid raft pools.

This article is protected by copyright. All rights reserved.



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Towards a bacterial treatment for armpit malodour

Abstract

Axillary malodour is a frustrating condition for many people. It can lead to significant discomforts and various psychological effects. The underarm microbiome generally plays a major role in axillary malodour formation. Not only the bacteria on the armpit epidermis, but especially those living in the sweat glands, sweat pores and hair follicles play a pivotal role in malodour development.

In order to treat underarm malodour, this viewpoint paper envisions a bacterial treatment. Replacing the autochthonous malodour causing microbiome with a non-odour causing microbiome, through an armpit bacterial transplantation or direct application of probiotics/non-odour causing bacteria could resolve the condition. Selective steering of the microbiome with prebiotics, biochemicals or plant extracts could likewise greatly help in improving the underarm odour. Elimination/inhibition of the 'bad bugs' and application/stimulation of the 'good bugs' should be part of the future treatment for axillary body odour.

This article is protected by copyright. All rights reserved.



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An Advanced Mouse Model for Human Skin Wound Healing

Abstract

Here we report a model for studying wound repair based on skin regenerated from human tissue culture-expanded cells. The reconstituted skin (hRSK) responds to injury similar to that of intact human skin, and its constituent cells contribute to the healing process. As we have demonstrrated that hRSK composed of GFP-labelled cells also heals "normally", we believe this model will be useful in analyzing the wound repair process using genetically modified human cells.

This article is protected by copyright. All rights reserved.



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SVEP1 plays a crucial role in epidermal differentiation

Abstract

SVEP1 is a recently identified multi-domain cell adhesion protein, homologous to the mouse polydom protein, which has been shown to mediate cell-cell adhesion in an integrin dependent-manner in osteogenic cells. In the present study, we characterized SVEP1 function in the epidermis. SVEP1 was found by qRT-PCR to be ubiquitously expressed in human tissues, including the skin. Confocal microscopy revealed that SVEP1 is normally mostly expressed in the cytoplasm of basal and suprabasal epidermal cells. Down-regulation of SVEP1 expression in primary keratinocytes resulted in decreased expression of major epidermal differentiation markers. Similarly, SVEP1 down-regulation was associated with disturbed differentiation and marked epidermal acanthosis in three-dimensional skin equivalents. In contrast, the dispase assay failed to demonstrate significant differences in adhesion between keratinocytes expressing normal vs. low levels of SVEP1. Homozygous Svep1 knockout mice were embryonic lethal. Thus, to assess the importance of SVEP1 for normal skin homeostasis in vivo, we down regulated SVEP1 in zebra fish embryos with a Svep1-specific splice morpholino. Scanning electron microscopy revealed a rugged epidermis with perturbed microridge formation in the center of the keratinocytes of morphant larvae. Transmission electron microscopy analysis demonstrated abnormal epidermal cell-cell adhesion with disadhesion between cells in Svep1-deficient morphant larvae compared to controls. In summary, our results indicate that SVEP1 plays a critical role during epidermal differentiation.

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Beside to bench: JAK-inhibitor ruxolitinib inhibits the expression of cytokines characteristic of cutaneous lupus erythematosus

Abstract

This study was stimulated by the clinical observation of a rapid response of a chilblain lupus patient to treatment with JAK1/2-kinase inhibitor ruxolitinib. We investigated the in-vivo expression of phospho-JAK2 in CLE skin samples as well as the immunomodulatory in-vitro effect of ruxolitinib in cultured immortalized keratinocytes and in a 3D human epidermis model (epiCS). Our results demonstrate that ruxolitinib significantly decreases the production of CLE-typical cytokines (CXCL10, CXCL9, MxA) and might be a promising drug for future clinical studies in patients with CLE and related autoimmune skin diseases.

This article is protected by copyright. All rights reserved.



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Saliva protein biomarkers to detect oral squamous cell carcinoma (OSCC)

Abstract

In a recent study published in the Proceedings of the National Academy of Sciences of the U.S.A., Jau-Song Yu et al reported of their generated four–protein biomarker panel consisting of MMP1, KNG1, ANXA2, and HSPA5, as based on a risk-score scheme they established (Yu et al, 2016). This panel showed high sensitivity (87.5%) and specificity (80.5%) values in a test set to distinguish OSCC patients' saliva samples from non-OSCC patients' saliva samples. The risk score >0.4 detected 84% of the stage I OSCCs and a significant portion (42%) of the high-risk, visible, oral potentially-malignant disorders (OPMDs). Moreover, among 88 high-risk OPMD patients with available follow-up results, 18 developed OSCC within 5 years; of these nearly 78% had risk scores >0.4. The authors concluded that their four-protein panel may, therefore, offer a clinically effective tool for detecting OSCC and monitoring high-risk OPMDs through a readily available bio-fluid (i.e. saliva).

This article is protected by copyright. All rights reserved.



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Anterior chamber exudation in chronic myeloid leukaemia

Anterior chamber leukaemic hypopyon is a rare occurrence in chronic myeloid leukaemia. We discuss two cases marked by rapid exudation inside the anterior chamber, which were subsequently diagnosed as chronic myeloid leukaemia. The hypopyon in both the cases resolved on induction of chemotherapy.



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Malignant melanoma of cervix

A 68-year-old woman presented with symptoms of bleeding per vaginum. On examination, a growth was seen in the cervix, clinically considered to be squamous cell carcinoma. The growth was confined to the cervix and did not involve the parametria. However, on biopsy it was diagnosed as malignant melanoma. She underwent surgery elsewhere and was advised chemotherapy as these tumours are aggressive; however, she refused chemotherapy. She has been on regular follow-up and has an ongoing survival and disease-free period of more than 5 years. Primary cervical malignant melanomas are very rare as compared with vulval and vaginal counterparts and should be considered in the histological differential diagnosis of poorly differentiated malignant neoplasms involving cervix. Moreover, it is important to rule out metastasis from common primary sites such as skin, oesophagus, uveal tract and anorectal region before considering diagnosis of primary cervical melanoma.



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Why so blue? A case of neonatal cyanosis due to congenital methaemoglobinaemia (HbM Iwate)

Description

A 2.18 kg male baby was born by elective caesarean section at 34+3 weeks to a primiparous mother with autosomal dominant congenital methaemoglobinaemia (HbM Iwate) and gestational diabetes. Having been asymptomatic throughout her life, she developed significant respiratory symptoms in the third trimester, possibly due to a superimposed acquired methaemoglobinaemia, which necessitated hospitalisation, red cell exchange and early delivery of her infant.

At birth, the baby remained cyanosed despite good respiratory effort, and congenital methaemoglobinaemia was presumed. However, he quickly developed moderate respiratory distress (presumably unrelated) and was managed with facial continuous positive airway pressure (CPAP) in the delivery room, demonstrating maximal preductal saturations of 73% in 100% oxygen.

In the neonatal unit, he was started on nasal high-flow therapy. Urgent echocardiography excluded heart disease, and chest X-ray was unremarkable. Saturation monitoring was deemed unreliable; therefore, respiratory support was weaned (and stopped within 48 hours) based on regular normal capillary...



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Unusual cause of pleuritic chest pain in a child

We present the case of a 5-year-old boy with hereditary multiple exostoses who presented with left-sided pleuritic chest pain. A CT scan of the chest revealed an intrathoracic exostosis in close association with the heart.



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VURD syndrome in an infant presenting with potentially fatal staphylococcal urinary tract infection and septicaemia

Description

A newborn (NB) boy was delivered at 39 weeks of gestation with 4160 g weight and an APGAR score of 8/9. The pregnancy was uneventful, with normal first and second trimester ultrasound. The third trimester ultrasound revealed an isolated right kidney hydronephrosis, a normal sized bladder without thickening of wall as well a normal amniotic fluid volume. Kidney and bladder ultrasound (KBU) scan performed 48 hours after birth showed persistence of right kidney hydronephrosis as well dilation of right ureter. The left kidney and ureter were normal and alteration in bladder volume, bladder wall thickness and posterior urethra were observed. Trimethoprim prophylaxis was started, and the NB was discharged home in good condition. At 1 month age he was revaluated and remained asymptomatic, with an appropriate weight gain. The parents reported normal micturition with good urinary stream, without straining or dribbling. No changes were found on physical examination and the bladder...



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Locking plate external fixation and negative pressure wound therapy for treatment of a primary infection in a closed clavicle fracture

Infection in a clavicle fracture is uncommon, but remains a challenging problem. A paucity of soft tissue coverage often combined with significant displacement and interfragmentary movement add complexity to an already difficult situation for effective infection treatment. External fixation in principle offers a means of achieving fracture stability, while the infection is being eradicated. We present the case of a closed clavicle fracture, initially treated conservatively, that presented 5 weeks later with infection. The fracture was definitively treated with external fixation using a locking plate positioned superficially to the skin, plus negative pressure wound therapy and subsequent secondary closure and antibiotic therapy. This case illustrates a novel method of treatment in this unusual presentation that was well tolerated by the patient and resulted in a good clinical outcome.



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Acquired male urethral diverticulum: a rare entity treated in a one-stage procedure

Acquired male urethral diverticulum is a rare entity with most of the literature revolving around case reports or small case series. Up to two-thirds of cases are acquired, mostly as a result of trauma, stricture or infection. Infrequently, some cases develop as a complication of urological procedures, or even penile clamping. We present the case of an adult male with lower urinary tract symptoms, recurrent urinary infections and a history of multiple surgeries to treat a complicated perineal fistulae disease. With the help of imaging techniques, a bulbar urethral diverticulum was discovered. Owing to the symptomatic nature of the diverticulum, an open procedure was performed with excision and primary urethral anastomosis. No urinary symptoms were reported and follow-up imaging and flowmetry demonstrated very good functional outcome.



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Anterior Hypopituitarism and Treatment Response in Hunter Syndrome: A Comparison of Two Patients

Hypopituitarism is a clinically important diagnosis and has not previously been reported in Hunter syndrome. We contrast two cases with anatomic pituitary anomalies: one with anterior panhypopituitarism and the other with intact pituitary function. Patient 1, a 10-year-old boy with Hunter syndrome, was evaluated for poor growth and an ectopic posterior pituitary gland. Endocrine testing revealed growth hormone (GH) deficiency, secondary adrenal insufficiency, and tertiary hypothyroidism. An improvement in growth velocity with hormone replacement (GH, thyroxine, and corticosteroid) was seen; however, final adult height remained compromised. Patient 2, a 13-year-old male with Hunter syndrome, was evaluated for growth failure. He had a large empty sella turcica with posteriorly displaced pituitary. Functional endocrine testing was normal and a trial of GH-treatment yielded no significant effect. Panhypopituitarism associated with pituitary anomalies has not been previously reported in Hunter syndrome and was an incidental finding of significant clinical importance. In the setting of documented anterior hypopituitarism, while hormone replacement improved growth velocity, final height remained impaired. In patient 2 with equivocal GH-testing results, treatment had no effect on linear growth. These cases highlight the importance of careful clinical assessment in Hunter syndrome and that judicious hormone replacement may be indicated in individual cases.

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Pembrolizumab and Lenvatinib in Treating Metastatic or Recurrent Differentiated Thyroid Cancer That Cannot Be Removed by Surgery

Conditions:   Columnar Cell Variant Thyroid Gland Papillary Carcinoma;   Follicular Variant Thyroid Gland Papillary Carcinoma;   Poorly Differentiated Thyroid Gland Carcinoma;   Recurrent Thyroid Gland Carcinoma;   Stage III Differentiated Thyroid Gland Carcinoma;   Stage III Thyroid Gland Follicular Carcinoma;   Stage III Thyroid Gland Papillary Carcinoma;   Stage IV Thyroid Gland Follicular Carcinoma;   Stage IV Thyroid Gland Papillary Carcinoma;   Stage IVA Differentiated Thyroid Gland Carcinoma;   Stage IVA Thyroid Gland Follicular Carcinoma;   Stage IVA Thyroid Gland Papillary Carcinoma;   Stage IVB Differentiated Thyroid Gland Carcinoma;   Stage IVB Thyroid Gland Follicular Carcinoma;   Stage IVB Thyroid Gland Papillary Carcinoma;   Stage IVC Differentiated Thyroid Gland Carcinoma;   Stage IVC Thyroid Gland Follicular Carcinoma;   Stage IVC Thyroid Gland Papillary Carcinoma;   Tall Cell Variant Thyroid Gland Papillary Carcinoma;   Thyroid Gland Oncocytic Follicular Carcinoma
Interventions:   Other: Laboratory Biomarker Analysis;   Drug: Lenvatinib;   Biological: Pembrolizumab
Sponsors:   Academic and Community Cancer Research United;   National Cancer Institute (NCI)
Not yet recruiting - verified November 2016

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Comparison of Concomitant Cisplatin Versus Carboplatin and 5-fluorouracil With Radiotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma

Condition:   Head and Neck Squamous Cell Carcinoma
Interventions:   Drug: cisplatin;   Drug: carboplatin;   Drug: 5-FU
Sponsors:   University Medical Center Groningen;   VU University Medical Center
Recruiting - verified November 2016

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Targeting of the WT1 91–138 fragment to human dendritic cells improves leukemia-specific T-cell responses providing an alternative approach to WT1-based vaccination

Abstract

Due to its immunogenicity and overexpression concomitant with leukemia progression, Wilms tumor protein 1 (WT1) is of particular interest for immunotherapy of AML relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). So far, WT1-specific T-cell responses have mainly been induced by vaccination with peptides presented by certain HLA alleles. However, this approach is still not widely applicable in clinical practice due to common limitations of HLA restriction. Dendritic cell (DC) vaccines electroporated with mRNA encoding full-length protein have also been tested for generating WT1-derived peptides for presentation to T-cells. Alternatively, an efficient and broad WT1 peptide presentation could be elicited by triggering receptor-mediated protein endocytosis of DCs. Therefore, we developed antibody fusion proteins consisting of an antibody specific for the DEC205 endocytic receptor on human DCs and various fragments of WT1 as DC-targeting recombinant WT1 vaccines (anti-hDEC205-WT1). Of all anti-hDEC205-WT1 fusion proteins designed for overcoming insufficient expression, anti-hDEC205-WT110–35, anti-hDEC205-WT191–138, anti-hDEC205-WT1223–273, and anti-hDEC205-WT1324–371 were identified in good yields. The anti-hDEC205-WT191–138 was capable of directly inducing ex vivo T-cell responses by co-incubation of the fusion protein-loaded monocyte-derived mature DCs and autologous T-cells of either healthy or HSCT individuals. Furthermore, the DC-targeted WT191–138-induced specific T-cells showed a strong cytotoxic activity by lysing WT1-overexpressing THP-1 leukemia cells in vitro while sparing WT1-negative hematopoietic cells. In conclusion, our approach identifies four WT1 peptide-antibody fusion proteins with sufficient production and introduces an alternative vaccine that could be easily translated into clinical practice to improve WT1-directed antileukemia immune responses after allo-HSCT.



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When the Patient Believes That the Organs Are Destroyed: Manifestation of Cotard’s Syndrome

Cotard's Syndrome (CS) is a rare clinical event described for the first time in 1880 by the neurologist and psychiatrist Jules Cotard and characterized by negation delusions (or nihilists). Immortality and hypochondriac delusions are also typical. Nowadays, it is known that CS can be associated with many neuropsychiatric conditions. In this article, we describe the case of a patient that believed not having more organs and having the body deformed and whose CS was associated with a bigger depressive disorder. Although the electroconvulsive therapy is the most described treatment modality in the literature, the reported case had therapeutic success with association of imipramine and risperidone.

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Volar Locking Plate Breakage after Nonunion of a Distal Radius Osteotomy

We report a 38-year-old male with a nonunion followed by plate breakage after volar plating of a distal radius osteotomy. Volar locking plates have added a new approach to the treatment of distal radius malunions, due to a lower morbidity of the surgical approach and the strength of the final construction, allowing early mobilization and return to function. Conclusion. Plate breakage is an uncommon complication of volar locking plate fixation. To our knowledge, few cases have been described after a distal radius fracture and no case has been described after a distal radius corrective osteotomy. In the present case, plate breakage appears to have occurred as a result of a combination of multiple factors as the large corrective lengthening osteotomy, the use of demineralized bone matrix instead of bone graft, and the inappropriate fixation technique as an unfilled screw on the osteotomy site, rather than the choice of plate.

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A Multi-Center Study on Anaphylaxis caused by Peanut, Tree Nuts and Seeds in Children and Adolescents

Abstract

Peanut (PN) and tree nuts (TNs) are common causes of anaphylaxis in Western countries but no information is available in Korea. To feature clinical characteristics of anaphylaxis caused by PN, TNs, and seeds, a retrospective medical record review was performed in 14 university hospitals in Korea (2009-2013).One hundred and twenty-six cases were identified, with the mean age of 4.9 years. PN, walnut (WN), and pine nut accounted for 32.5%, 41.3%, and 7.1%, respectively. The median values of specific IgE (sIgE) to PN, WN and pine nut were 10.50 kUA/L, 8.74 kUA/Land 4.61 kUA/L, respectively. Among 50 cases managed in the emergency department, 52.0% were treated with epinephrine, 66.0% with steroid, 94.0% with antihistamines, 36.0% with oxygen, and 48.0% with bronchodilator. In conclusion, WN, PN and pine nut were the 3 most common triggers of anaphylaxis in Korean children and anaphylaxis could occur at remarkably low levels of sIgE.

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From the Medical Board of the National Psoriasis Foundation: Treatment targets for plaque psoriasis

An urgent need exists in the United States to establish treatment goals in psoriasis.

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Intra-Attack Vestibuloocular Reflex Changes in Ménière’s Disease

Ménière's attack has been shown to temporarily alter the vestibuloocular reflex (VOR). A patient with unilateral Ménière's disease was serially evaluated with the video Head Impulse Test during single, untreated episodes of acute vertigo. Spontaneous nystagmus activity was concurrently recorded in order to establish the three typical phases of Ménière's attack (irritative, paralytic, and recovery) and correlate them with VOR performance. The onset of attack was associated with a quick change in VOR gain on the side of the affected ear. While a rapidly progressive reduction of the VOR was evident at the paralytic nystagmus phase, in the recovery phase the VOR gain returned to normal and the direction of the previous nystagmus reversed. The membrane rupture potassium intoxication theory provides a good foundation with which to explain these dynamic VOR changes and the observed triphasic direction behavior of the spontaneous nystagmus. We additionally postulated that endolymphatic fluid displacement could have a synergic effect during the earliest phase of attack.

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Human papillomavirus–induced oropharyngeal cancer in Hispanics in the United States

Objectives/Hypothesis

Determine disparities in survival outcome and clinical presentation between Hispanic and non-Hispanic white patients with human papillomavirus–positive oropharyngeal squamous cell carcinoma.

Study Design

Retrospective clinical research.

Methods

Clinical data on Hispanics and non-Hispanic white patients with diagnosis of human papillomavirus/p16–positive oropharyngeal squamous cell carcinoma were drawn from a tumor registry from the University of Miami Hospitals and Clinics from 2008 to 2014.

Of 436 patients with oropharyngeal squamous cell carcinoma, 237 patents met inclusion criteria. Patient's age, gender, smoking history, alcohol history, race/ethnicity, tumor T stage, nodal N stage, and composite TNM stage were included in the analysis. Associations between race and other categorical variables were explored with χ2 test or Fisher exact test where appropriate. Survival curves were generated using the Kaplan-Meier method.

Results

Significant differences in clinical presentation was detected between Hispanic (N = 70) and non-Hispanic white (N = 167) patients. Hispanic human papillomavirus–positive oropharyngeal squamous cell carcinoma patients showed a higher proportion of women with disease, a higher proportion of patients presenting with tonsil rather than tongue base primary subsite cancer, and a higher proportion of patients who do not consume alcohol compared to non-Hispanic white human papillomavirus–positive oropharyngeal squamous cell carcinoma patients. A statistically significant survival difference between these two ethnic groups was not detected in the current dataset.

Conclusions

Unique differences in clinical presentations between Hispanic patients and non-Hispanic whites with human papillomavirus–positive oropharyngeal squamous cell carcinoma were detected. This may be the first study to report novel clinical presentation in Hispanic human papillomavirus–positive patients with oropharyngeal squamous cell carcinoma living in the United States.

Level of Evidence

4. Laryngoscope, 2016



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